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PXD017317

PXD017317 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePolypharmacological perturbation of the 14-3-3 adaptor protein interactome stimulates neurite outgrowth
DescriptionTargeting protein-protein interactions (PPIs) is a promising, but under-exploited, approach in the development of drugs for many indications. 14-3-3 proteins are a family of adaptor molecules with ubiquitous and critical functions in dozens of cell signaling networks. 14-3-3s bind to hundreds of ‘client proteins’ in a stereotyped fashion, altering client protein function, localization and stability. 14-3-3s are especially abundant in the central nervous system, and the small molecule fusicoccin-A (FC-A), a tool compound that can be used to manipulate 14-3-3 PPIs, enhances neurite outgrowth in cultured neurons. New semisynthetic FC-A derivatives with improved binding affinity for 14-3-3 complexes have recently been developed. Here we employ a series of screens that identify these compounds as potent inducers of neurite outgrowth through a polypharmacological mechanism. Using proteomics and x-ray crystallography, we discover that these compounds extensively perturb the 14-3-3 interactome through a unique and previously undescribed mechanism involving direct stabilization and inhibition of 14-3-3 PPIs. These results provide new insights into the development of drugs to target 14-3-3 PPIs, a potential therapeutic strategy for CNS diseases.
HostingRepositoryPRIDE
AnnounceDate2020-03-31
AnnouncementXMLSubmission_2020-03-30_23:45:22.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD017317
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterSara Luiza Banerjee
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListPhospho; Deamidated; phosphorylated residue; Oxidation; monohydroxylated residue; Carbamidomethyl; iodoacetamide derivatized residue; deamidated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-01-29 04:03:40ID requested
12020-03-30 23:45:23announced
Publication List
Kaplan A, Andrei SA, van Regteren Altena A, Simas T, Banerjee SL, Kato N, Bisson N, Higuchi Y, Ottmann C, Fournier AE, Polypharmacological Perturbation of the 14-3-3 Adaptor Protein Interactome Stimulates Neurite Outgrowth. Cell Chem Biol, 27(6):657-667.e6(2020) [pubmed]
Keyword List
submitter keyword: Polypharmacology, axon, 14-3-3, regeneration, Rap1
Contact List
Nicolas Bisson
contact affiliationCentre de recherche du Centre Hospitalier Universitaire (CHU) de Quebec-Université Laval, Québec, QC, Canada Centre de recherche sur le cancer de l’Université Laval, Québec, QC, Canada PROTEO-Quebec Network for Research on Protein Function, Engineering, and Applications, Québec, QC, Canada Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Québec, QC, Canada
contact emailNick.Bisson@crchudequebec.ulaval.ca
lab head
Sara Luiza Banerjee
contact affiliationCentre de recherche sur le cancer – Université Laval
contact emailbanerjee.sara@gmail.com
dataset submitter
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